A novel, complex heterozygous mutation within Gsalpha gene in patient with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is caused by embryonic somatic mutations leading to the substitution of His or Cys for Arg at amino acid 201 of the alpha-subunit of the signal transduction protein Gs (Gsalpha). The mutations have been found in many affected tissues of patients with MAS. Recently, a new missense mutation was detected in a patient with MAS, leading to the substitution of glycine for arginine at amino acid 201 of the Gsalpha gene, whereas no mutations have been reported at other sites in this gene. In the present study, we identified the activating mutations in the gene encoding Gsalpha protein in the osseous lesions of fibrous dysplasia and peripheral blood leukocyte in a 17-yr-old male patient with MAS. In addition, a heterozygous mutation encoding substitution of Arg201 of Gsalpha with His was found. Interestingly, we also found the other two types of mutations within the Gsalpha gene in the patient's affected osseous tissue. One is a combination mutation in the same allele at codons 209 and 210 of the Gsalpha gene, and the other the missense mutation at codon 235.